Genome-wide Association Study for Urinary and Fecal Incontinence in Women.

Urinary incontinence (UI) and fecal incontinence (FI) are common disorders in women that negatively impact quality of life. In addition to known health and lifestyle risk factors, genetics may play a role. Identification of genetic variants associated with UI and FI could result in better understanding of etiologic pathways and new interventions and treatments.

We previously generated genome-wide single nucleotide polymorphism (SNP) data from Nurses' Health Studies participants. The participants provided longitudinal UI and FI information via questionnaires. Cases of UI (n=6120) reported at least weekly UI on a majority of questionnaires (3 or 4 across 12-16 years); controls (n=4811) consistently reported little to no UI. We classified women with UI into stress (n=1809), urgency (n=1942), and mixed (n=2036) subtypes. Cases of FI (n=4247) reported at least monthly FI on a majority of questionnaires; controls (n=11634) consistently reported no FI. We performed a genome-wide association study (GWAS) for each incontinence outcome.

We identified 8 SNPs significantly associated (p<5x10-8) with UI, located in two loci, chromosome 8q23.3 and 1p32.2. There were no genome-wide significant findings for the UI subtype analyses; however, the significant associations for overall UI were stronger for the urgency and mixed subtypes than for stress. While no SNP reached genome-wide significance for FI, four SNPs had p<10-6.

Few studies have collected both genetic data and detailed UI and FI information. This GWAS provides initial evidence of genetic associations for UI and merits further research to replicate our findings and identify additional risk variants.

The Journal of urology. 2019 Nov 15 [Epub ahead of print]

Kathryn L Penney, Mary K Townsend, Constance Turman, Kimberly Glass, Kyle Staller, Peter Kraft, Francine Grodstein, Vatche A Minnassian

Department of Medicine, Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts., Cancer Epidemiology Department, Moffitt Cancer Center, Tampa, Florida., Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts., Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts., Division of Urogynecology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts.